Diabetes and Advanced Glycoxidation End-Products

  • Melpomeni Peppa
  • Jaime Uribarri
  • Helen Vlassara
Part of the Contemporary Cardiology book series (CONCARD)


The incidence of diabetes, especially type 2 diabetes, is increasing at an alarming rate assuming epidemic proportions (1). Worldwide, 124 million people had diabetes by 1997, although an estimated 221 million people will have diabetes by the year 2010 (1).


Diabetic Nephropathy Diabetic Retinopathy Glycated Albumin Advanced Glycation Endproducts Glycoxidation Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications estimates and projections to the year 2010. Diabet Med 1997;14(Suppl 5):S1–S85.PubMedGoogle Scholar
  2. 2.
    DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977.CrossRefGoogle Scholar
  3. 3.
    Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837–853.Google Scholar
  4. 4.
    Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414(6865):813–820.PubMedCrossRefGoogle Scholar
  5. 5.
    Vlassara H, Palace MR. Diabetes and advanced glycation endproducts. J Intern Med 2002;251(2):87–101.PubMedCrossRefGoogle Scholar
  6. 6.
    Thorpe SR, Baynes JW. Role of the Maillard reaction in diabetes mellitus and diseases of aging. Drugs Aging 1996;9(2):69–77.PubMedGoogle Scholar
  7. 7.
    Miyata T, Ishikawa S, Asahi K, et al. 2-Isopropylidenehydrazono-4-oxo-thiazolidin-5-phenylacetanilide (OPB-9195) treatment inhibits the development of intimal thickening after balloon injury of rat carotid artery: role of glycoxidation and lipoxidation reactions in vascular tissue damage. FEBS Lett 1999;445(1):202–206.PubMedCrossRefGoogle Scholar
  8. 8.
    Wolffenbuttel BH, Boulanger CM, Crijns FR, et al. Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 1998;95(8):4630–4634.PubMedCrossRefGoogle Scholar
  9. 9.
    Kass DA, Sapiro EP, Kawaguchi M, et al. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 2001;104:1464–1470.PubMedCrossRefGoogle Scholar
  10. 10.
    Nakayama M, Izumi G, Nemoto Y, et al. Suppression of N(epsilon)-(carboxymethyl)lysine generation by the antioxidant N-acetylcysteine. Perit Dial Int 1999;19(3):207–210.PubMedGoogle Scholar
  11. 11.
    Soulis T, Sastra S, Thallas V, et al. A novel inhibitor of advanced glycation end-product formation inhibits mesenteric vascular hypertrophy in experimental diabetes. Diabetologia 1999;42(4):472–479.PubMedCrossRefGoogle Scholar
  12. 12.
    Asif M, Egan J, Vasan S, et al. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci USA 2000;97(6):2809–2813.PubMedCrossRefGoogle Scholar
  13. 13.
    Vasan S, Foiles PG, Founds, HW. Therapeutic potential of AGE inhibitors and breakers of AGE protein cross-links. Expert Opin Investig Drugs 2001;10(11):1977–1987.PubMedCrossRefGoogle Scholar
  14. 14.
    Suarez G, Rajaram R, Oronsky AL, Gawinowicz MA. Nonenzymatic glycation of bovine serum albumin by fructose (fructation). Comparison with the Maillard reaction initiated by glucose. J Biol Chem 1989;264(7):3674–3679.PubMedGoogle Scholar
  15. 15.
    Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem 1996;271(17):9982.PubMedCrossRefGoogle Scholar
  16. 16.
    Wolff SP, Dean RT. Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes. Biochem J 1987;245(1):243–250.PubMedGoogle Scholar
  17. 17.
    Dunn JA, Ahmed MU, Murtiashaw MH, et al. Reaction of ascorbate with lysine and protein under autoxidizing conditions: formation of N epsilon-(carboxymethyl)lysine by reaction between lysine and products of autoxidation of ascorbate. Biochemistry 1990;29(49):10964–10970.PubMedCrossRefGoogle Scholar
  18. 18.
    Hunt JV, Simpson JA, Dean RT. Hydroperoxide-mediated fragmentation of proteins. Biochem J 1988;250(1):87–93.PubMedGoogle Scholar
  19. 19.
    Thornalley PJ, Langborg A, Minhas HS. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 1999;344(1):109–116.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee T, Kimiagar M, Pintauro SJ, Chichester CO. Physiological and safety aspects of Maillard browning of foods. Prog Food Nutr Sci 1981;5:243–256.PubMedGoogle Scholar
  21. 21.
    O’Brien J, Morrissey PA. Nutritional and toxicological aspects of the Maillard browning reaction in foods. Crit Rev Food Sci Nutr 1989;28:211–248.PubMedGoogle Scholar
  22. 22.
    Pellegrino L, Cattaneo SOccurrence of galactosyl isomaltol and galactosyl beta-pyranone in commercial drinking milk. Nahrung 2001;45(3):195–200.PubMedCrossRefGoogle Scholar
  23. 23.
    Henle T. A food chemist’s view of advanced glycation end-products. Perit Dial Int 2001;21(Suppl 3):S125–S130.PubMedGoogle Scholar
  24. 24.
    Koschinsky T, He CJ, Mitsuhashi T, et al. Orally absorbed reactive advanced glycation end products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 1997;94:6474–6479.PubMedCrossRefGoogle Scholar
  25. 25.
    He C, Sabol J, Mitsuhashi T, Vlassara H. Dietary glycotoxins: Inhibition of reactive products by aminoguanidine facilitates renal clearance and reduces tissue sequestration. Diabetes 1999;48:1308–1315.PubMedCrossRefGoogle Scholar
  26. 26.
    Cai W, Cao Q, Zhu L, Peppa M, He C, Vlassara H. Oxidative stress-inducing carbonyl compounds from common foods: Novel mediators of cellular dysfunction. Mol Med 2002;8(7):337–346.PubMedGoogle Scholar
  27. 27.
    Zheng F, He C, Cai W, Hattori M, Steffes M, Vlassara H. Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products. Diabetes Metab Res Rev 2002;18(3):224–237.PubMedCrossRefGoogle Scholar
  28. 28.
    Lin RY, Reis ED, Dore AT, et al. Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice. Atherosclerosis 2002;163(2):303–311.PubMedCrossRefGoogle Scholar
  29. 29.
    Lin RY, Choudhury RP, Cai W, et al. Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 2003;168:213–220.PubMedCrossRefGoogle Scholar
  30. 30.
    Peppa M, Brem H, Ehrlich P, et al. Adverse effects of dietary glycotoxins in genetically diabetic mice. Diabetes 2003;52:2805–2813.PubMedCrossRefGoogle Scholar
  31. 31.
    Sebekova K, Faist V, Hofmann T, Schinzel R, Heidland A. Effects of a diet rich in advanced glycation end products in the rat remnant kidney model. Am J Kidney Dis 2003;41(3 Suppl 1):S48–S51PubMedGoogle Scholar
  32. 32.
    Peppa M, He C, Hattori M, et al. Fetal or neonatal low-glycotoxin environment prevents autoimmune diabetes in NOD mice. Diabetes 2003;52(6):1441–1448.PubMedCrossRefGoogle Scholar
  33. 33.
    Hofmann SM, Dong HJ, Li Z, et al. Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse. Diabetes 2002;51(7):2082–2089.PubMedCrossRefGoogle Scholar
  34. 34.
    Vlassara H, Cai W, Crandall J, et al. Inflammatory markers are induced by dietary glycotoxins: A pathway for accelerated atherosclerosis in diabetes. Proc Natl Acad Sci 2002;99(24):15,596–15,601.PubMedCrossRefGoogle Scholar
  35. 35.
    Uribarri J, Peppa M, Cai W, et al. Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. J Am Kid Dis 2003;42(3):532–538.CrossRefGoogle Scholar
  36. 36.
    Uribarri J, Peppa M, Cai W, et al. Restriction of dietary glycotoxins markedly reduces AGE toxins in renal failure patients. J Am Soc Nephrol 2003;14(3):728–731.PubMedCrossRefGoogle Scholar
  37. 37.
    Peppa M, Uribarri J, Cai W, Lu M, Vlassara H. Glycoxidation and inflammation in renal failure patients. J Am Kid Dis 2004;43(4):690–696.CrossRefGoogle Scholar
  38. 38.
    Swedko PJ, Clark HD, Paramsothy K, Akbari A. Serum creatinine is an inadequate screening test for renal failure in elderly patients. Arch Intern Med 2003;163:356–360.PubMedCrossRefGoogle Scholar
  39. 39.
    Nicholl ID, Bucala R. Advanced glycation endproducts and cigarette smoking. Cell Mol Biol (Noisy-le-grand) 1998;44(7):1025–1033.Google Scholar
  40. 40.
    Nicholl ID, Stitt AW, Moore JE, et al. Increased levels of advanced glycation endproducts in the lenses and blood vessels of cigarette smokers. Mol Med 1998;4(9):594–601.PubMedGoogle Scholar
  41. 41.
    Vlassara H. The AGE-receptor in the pathogenesis of diabetic complications. Diabetes Metab Res Rev 2001;17(6):436–443.PubMedCrossRefGoogle Scholar
  42. 42.
    Gardiner TA, Stitt AW, Archer DB. Retinal vascular endothelial cell endocytosis increases in early diabetes. Lab Invest 1995;72(4):439–444.PubMedGoogle Scholar
  43. 43.
    Sano H, Higashi T, Matsumoto K, et al. Insulin enhances macrophage scavenger receptor-mediated endocytic uptake of advanced glycation end products. J Biol Chem 1998;273(15):8630–8637.PubMedCrossRefGoogle Scholar
  44. 44.
    Miyata T, Ueda Y, Shinzato T, et al. Accumulation of albumin-linked and free-form pentosidine in the circulation of uremic patients with end-stage renal failure: renal implications in the pathophysiology of pentosidine. J Am Soc Nephrol 1996;7(8):1198–1206.PubMedGoogle Scholar
  45. 45.
    Makita Z, Radoff S, Rayfield EJ, et al. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991, 325(12):836–842.PubMedCrossRefGoogle Scholar
  46. 46.
    Uribarri J, Cai W, Peppa M, Goldberg T, Vlassara H. Renal clearance of advanced glycoxidation end products (AGE) is markedly reduced in diabetic patients in the absence of impaired GFR. J Am Soc Nephrol 2003;14:394A.CrossRefGoogle Scholar
  47. 47.
    Shinohara M, Thornalley PJ, Giardino I, et al. Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 1998;101(5):1142–1147.PubMedGoogle Scholar
  48. 48.
    Bucala R, Mitchell R, Arnold K, Innerarity T, Vlassara H, Cerami A. Identification of the major site of apolipoprotein B modification by advanced glycosylation end products blocking uptake by the low density lipoprotein receptor. J Biol Chem 1995;270(18):10,828–10,832.PubMedCrossRefGoogle Scholar
  49. 49.
    Giardino I, Edelstein D, Brownlee M. Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J Clin Invest 1994;94(1):110–117.PubMedGoogle Scholar
  50. 50.
    Li YM, Mitsuhashi T, Wojciechowicz D, et al. Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80K-H membrane proteins. Proc Natl Acad Sci USA 1996;93(20):11,047–11,052.PubMedCrossRefGoogle Scholar
  51. 51.
    He CJ, Koschinsky T, Buenting C, Vlassara H. Presence of diabetic complications in type 1 diabetic patients correlates with low expression of mononuclear cell AGE-receptor-1 and elevated serum AGE. Mol Med 2001;7(3):159–168.PubMedGoogle Scholar
  52. 52.
    He CJ, Zheng F, Stitt A, et al. Differential expression of renal AGE-receptor genes in NOD mice: possible role in nonobese diabetic renal disease. Kidney Int 2000;58(5):1931–1940.PubMedCrossRefGoogle Scholar
  53. 53.
    Lu CY, He C, Cai W, Vlassara H. Overexpression of AGE-R1 inhibition AGE-induced MAPK and NF-kB activation in murine mesangial cells. Diabetes 2003;52(Suppl 1):A50.Google Scholar
  54. 54.
    Vlassara H, Li YM, Imani F, et al. Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex. Mol Med 1995;1(6):634–646.PubMedGoogle Scholar
  55. 55.
    Pugliese G, Pricci F, Leto G, et al. The diabetic milieu modulates the advanced glycation end product-receptor complex in the mesangium by inducing or upregulating galectin-3 expression. Diabetes 2000;49(7):1249–1257.PubMedCrossRefGoogle Scholar
  56. 56.
    Zhu W, Sano H, Nagai R, Fukuhara K, Miyazaki A, Horiuchi S. The role of galectin-3 in endocytosis of advanced glycation end products and modified low density lipoproteins. Biochem Biophys Res Commun 2001;280(4):1183–1188.PubMedCrossRefGoogle Scholar
  57. 57.
    Pricci F, Leto G, Amadio L, et al. Role of galectin-3 as a receptor for advanced glycosylation end products. Kidney Int 2000;Suppl 77:S31–S39.CrossRefGoogle Scholar
  58. 58.
    Pugliese G, Pricci F, Iacobini C, et al. Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. FASEB J 2001;15(13):2471–2479.PubMedCrossRefGoogle Scholar
  59. 59.
    Schmidt AM, Yan SD, Wautier JL, Stern D. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 1999;84(5):489–497.PubMedGoogle Scholar
  60. 60.
    Yamamoto Y, Kato I, Doi T, et al. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest 2001;108(2):261–268.PubMedCrossRefGoogle Scholar
  61. 61.
    Goova MT, Li J, Kislinger T, et al. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol 2001;159(2):513–525.PubMedGoogle Scholar
  62. 62.
    Brett J, Schmidt AM, Yan SD, et al. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 1993;143(6):1699–1712.PubMedGoogle Scholar
  63. 63.
    Sano H, Nagai R, Matsumoto K, Horiuchi S. Receptors for proteins modified by advanced glycation endproducts (AGE)—their functional role in atherosclerosis. Mech Ageing 1999;107(3):333–346.CrossRefGoogle Scholar
  64. 64.
    Ohgami N, Nagai R, Ikemoto M, et al. CD36, serves as a receptor for advanced glycation endproducts (AGE). J Diabetes Complications 2002;16(1):56–59.PubMedCrossRefGoogle Scholar
  65. 65.
    Ohgami N, Nagai R, Miyazaki A, et al. Scavenger receptor class B type I-mediated reverse cholesterol transport is inhibited by advanced glycation end products. J Biol Chem 2001;276(16):13,348–13,355.PubMedCrossRefGoogle Scholar
  66. 66.
    Sawamura T, Kume N, Aoyama T, et al. An endothelial receptor for oxidized low-density lipoprotein. Nature 1997;386(6620):73–77.PubMedCrossRefGoogle Scholar
  67. 67.
    Dachi H, Tsujimoto M, Arai H, Inoue K. Expression cloning of a novel scavenger receptor from human endothelial cells. J Biol Chem 1997;272(50):31217–31220.CrossRefGoogle Scholar
  68. 68.
    Li YM, Tan AX, Vlassara H. Antibacterial activity of lysozyme and lactoferrin is inhibited by binding of advanced glycation-modified proteins to a conserved motif. Nat Med 1995;1(10):1057–1061.PubMedCrossRefGoogle Scholar
  69. 69.
    Zheng F, Cai W, Mitsuhashi T, Vlassara H. Lysozyme enhances renal excretion of advanced glycation endproducts in vivo and suppresses adverse age-mediated cellular effects in vitro: a potential AGE sequestration therapy for diabetic nephropathy? Mol Med 2001;7(11):737–747.PubMedGoogle Scholar
  70. 70.
    Higashi T, Sano H, Saishoji T, et al. The receptor for advanced glycation end products mediates the chemotaxis of rabbit smooth muscle cells. Diabetes 1997;46(3):463–472.PubMedCrossRefGoogle Scholar
  71. 71.
    Poirier O, Nicaud V, Vionnet N, et al. Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients. Diabetes 2001;50(5):1214–1218.PubMedCrossRefGoogle Scholar
  72. 72.
    Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis 1999;34(5):795–808.PubMedGoogle Scholar
  73. 73.
    Osterby R, Anderson MJF, Gundersen HJG, Jorgensen HE, Mogensen CE, Parving HH Quantitative study on glomerular ultrastructure in type I diabetes with incipient nephropathy. Diab Nephrop 1983;3:95–100.Google Scholar
  74. 74.
    Skolnik E Y, Yang Z, Makita Z, et al. Human and rat mesangial cell receptors for glucose modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy. J Exp Med 1991;174:931–939.PubMedCrossRefGoogle Scholar
  75. 75.
    Doi T, Vlassara H, Kirstein M, Yamada Y Striker GE, Striker LJ. Receptor specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet derived growth factor. Proc Natl Acad Sci USA 1992;89:2873–2877.PubMedCrossRefGoogle Scholar
  76. 76.
    Scivittaro V, Ganz MB, Weiss MF. AGEs induce oxidative stress and activate protein kinase C-beta(II) in neonatal mesangial cells. Am J Physiol Renal Physiol 2000;278(4):F676–F683.PubMedGoogle Scholar
  77. 77.
    Doublier S, Salvidio G, Lupia E, et al. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II. Diabetes 2003;52(4):1023–1030.PubMedCrossRefGoogle Scholar
  78. 78.
    Yamagishi S, Inagaki Y, Okamoto T, et al. Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human-cultured mesangial cells. J Biol Chem 2002;277(23):20309–20315.PubMedCrossRefGoogle Scholar
  79. 79.
    Cohen MP, Wu VY, Cohen JA. Glycated albumin stimulates fibronectin and collagen IV production by glomerular endothelial cells under normoglycemic conditions. Biochem Biophys Res Commun 1997;239(1):91–94.PubMedCrossRefGoogle Scholar
  80. 80.
    Bendayan M. Immunocytochemical detection of advanced glycated end products in rat renal tissue as a function of age and diabetes. Kidney Int 1998;54(2):438–447.PubMedCrossRefGoogle Scholar
  81. 81.
    Gugliucci A, Bendayan M. Reaction of advanced glycation endproducts with renal tissue from normal and streptozotocin induced rats an ultrastructural study using colloidal gold cytochemistry. J Histochem. Cytochem 1995;43–6:591–600.Google Scholar
  82. 82.
    Yang CW, Vlassara H, Peten EP, He CJ, Striker GE, Striker LJ. Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease. Proc Natl Acad Sci USA 1994;91(20):9436–9440.PubMedCrossRefGoogle Scholar
  83. 83.
    Vlassara H, Fuh H, Makita Z, Krungkrai S, Cerami A, Bucala R. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and ageing complications. Proc Natl Acad Sci USA 1992;89:12043–12047.PubMedCrossRefGoogle Scholar
  84. 84.
    Soulis T, Cooper ME, Vranes D, Bucala R, Jerums G. Effects of aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment. Kidney Int 1996;50–2:627–634.CrossRefGoogle Scholar
  85. 85.
    Bach LA, Dean R, Youssef S, Cooper ME. Aminoguanidine ameliorates changes in the IGF system in experimental diabetic nephropathy. J Am Soc Nephrol 2001;12–10:2098–2107.Google Scholar
  86. 86.
    Osicka TM, Yu Y, Lee V, Panagiotopoulos S, Kemp BE, Jerums G. Aminoguanidine and ramipril prevent diabetes-induced increases in protein kinase C activity in glomeruli, retina and mesenteric artery. Clin Sci (Lond) 2001;100–3:249–257.Google Scholar
  87. 87.
    Kelly DJ, Gilbert RE, Cox AJ, Soulis T, Jerums G, Cooper ME. Aminoguanidine ameliorates overexpression of prosclerotic growth factors and collagen deposition in experimental diabetic nephropathy. J Am Soc Nephrol 2001;12(10):2098–2107.PubMedGoogle Scholar
  88. 88.
    Sharma K, Ziyadeh FN. Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes 1995;44(10):1139–1146.PubMedCrossRefGoogle Scholar
  89. 89.
    Forbes JM, Thallas V, Thomas MC, Jerums G, Cooper ME. Renoprotection is afforded by the advanced glycation end product (AGE) cross-link breaker, ALT-711. FASEB J 2003;17(12):1762–1764.PubMedGoogle Scholar
  90. 90.
    Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997;99(3):457–468.PubMedGoogle Scholar
  91. 91.
    Horie K, Miyata T, Maeda K, et al. Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. J Clin Invest 1997;100(12):2995–3004.PubMedGoogle Scholar
  92. 92.
    Sugiyama S, Miyata T, Horie K, et al. Advanced glycation end-products in diabetic nephropathy. Nephrol Dial Transplant. 1996;11(Suppl 5):91–94.PubMedGoogle Scholar
  93. 93.
    Tanji N, Markowitz GS, Fu C, et al. Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. J Am Soc Nephrol 2000;11(9):1656–1666.PubMedGoogle Scholar
  94. 94.
    Miura J, Yamagishi S, Uchigata Y, et al. Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes. J Diabetes Complications 2003;17(1):16–21.PubMedCrossRefGoogle Scholar
  95. 95.
    Sheetz MJ, King GL. Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA 2002;27;288(20):2579–2588.PubMedCrossRefGoogle Scholar
  96. 96.
    Kahn HA, Moorhead HB. Statistics on blindness in the model reporting area 1969–1970 US. Department of Health, Education, and Welfare Publication No. (NIH) US. Government Printing Office, Washington, 1973, pp. 73–427.Google Scholar
  97. 97.
    Chappey O, Dosquet C, Wautier MP, Wautier JL. Advanced glycation end products, oxidant stress and vascular lesions. Eur J Clin Invest 1997;27(2):97–108.PubMedCrossRefGoogle Scholar
  98. 98.
    Yamagishi S, Hsu CC, Taniguchi M, et al. Receptor-mediated toxicity to pericytes of advanced glycosylation end products: a possible mechanism of pericyte loss in diabetic microangiopathy. Biochem Biophys Res Commun 1995;213(2):681–687.PubMedCrossRefGoogle Scholar
  99. 99.
    Mamputu JC, Renier G. Advanced glycation end products increase, through a protein kinase C-dependent pathway, vascular endothelial growth factor expression in retinal endothelial cells. Inhibitory effect of gliclazide. J Diabetes Complications 2002;16(4):284–293.PubMedCrossRefGoogle Scholar
  100. 100.
    Reber F, Geffarth R, Kasper M, et al. Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection. Graefes Arch Clin Exp Ophthalmol 2003;241(3):213–225.PubMedGoogle Scholar
  101. 101.
    Chakravarthy U, Hayes RG, Stitt AW, McAuley E, Archer DB. Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products. Diabetes 1998;47:945–952.PubMedCrossRefGoogle Scholar
  102. 102.
    Sulochana KN, Ramprasad S, Coral K, et al. Glycation and glycoxidation studies in vitro on isolated human vitreous collagen. Med Sci Monit 2003;9(6):BR219–BR223.Google Scholar
  103. 103.
    Stitt AW, Li YM, Gardiner TA, Bucala R, Archer DB, Vlassara H. Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats. Am J Pathol 1997;150(2):523–531.PubMedGoogle Scholar
  104. 104.
    Clements RS Jr, Robison WG Jr, Cohen MP. Anti-glycated albumin therapy ameliorates early retinal microvascular pathology in db/db mice. J Diabetes Comp 1998;12:28–33.CrossRefGoogle Scholar
  105. 105.
    Xu X, Li Z, Luo D, et al. Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2003;241(1):56–62.PubMedGoogle Scholar
  106. 106.
    Wautier MP, Massin P, Guillausseau PJ, et al. N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients. Diabetes Metab 2003;29(1):44–52.PubMedCrossRefGoogle Scholar
  107. 107.
    Matsumoto Y, Takahashi M, Chikuda M, Arai K Levels of mature cross-links and advanced glycation end product cross-links in human vitreous. Jpn J Ophthalmol 2002;46(5):510–517.PubMedCrossRefGoogle Scholar
  108. 108.
    Koga K, Yamagishi S, Okamoto T, et al. Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction. Int J Clin Pharmacol Res 2002;22(1):13–17.PubMedGoogle Scholar
  109. 109.
    Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993;43(4):817–824.PubMedGoogle Scholar
  110. 110.
    Dyck PJ, Giannini C. Pathologic alterations in the diabetic neuropathies of humans: a review. J Neuropathol Exp Neurol 1996;55(12):1181–1193.PubMedGoogle Scholar
  111. 111.
    Boel E, Selmer J, Flodgaard HJ, Jensen T. Diabetic late complications: will aldose reductase inhibitors or inhibitors of advanced glycosylation endproduct formation hold promise? J Diabetes Complications 1995;9(2):104–129.PubMedCrossRefGoogle Scholar
  112. 112.
    Poduslo JF, Curran GL. Increased permeability across the blood-nerve barrier of albumin glycated in vitro and in vivo from patients with diabetic polyneuropathy. Proc Natl Acad Sci USA 1992;89(6):2218–2222.PubMedCrossRefGoogle Scholar
  113. 113.
    Poduslo JF, Curran GL. Glycation increases the permeability of proteins across the blood-nerve and blood-brain barriers. Brain Res Mol Brain Res 1994;23(1–2):157–162.PubMedCrossRefGoogle Scholar
  114. 114.
    Cullum NA, Mahon J, Stringer K, McLean WG. Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus. Diabetologia 1991;34(6):387–389.PubMedCrossRefGoogle Scholar
  115. 115.
    McLean WG. The role of axonal cytoskeleton in diabetic neuropathy. Neurochem Res 1997;22(8):951–956.PubMedCrossRefGoogle Scholar
  116. 116.
    Graham AR, Johnson PC. Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy. Ann Neurol 1985;17(5):450–454.PubMedCrossRefGoogle Scholar
  117. 117.
    Sugimoto K, Nishizawa Y, Horiuchi S, Yagihashi S. Localization in human diabetic peripheral nerve of N (epsilon)-carboxymethyllysine-protein adducts, an advanced glycation endproduct. Diabetologia 1997;40(12):1380–1387.PubMedCrossRefGoogle Scholar
  118. 118.
    Vlassara H, Brownlee M, Cerami A. Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus. Proc Natl Acad Sci USA 1981;78(8):5190–5192.PubMedCrossRefGoogle Scholar
  119. 119.
    Monnier VM, Bautista O, Kenny D, et al. Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial. Diabetes 1999;48(4):870–880.Google Scholar
  120. 120.
    Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997;99(3):457–468.PubMedGoogle Scholar
  121. 121.
    Beisswenger PJ, Makita Z, Curphey TJ, et al. Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes. Diabetes 1995;44(7):824–829.PubMedCrossRefGoogle Scholar
  122. 122.
    Watala C, Golanski J, Witas H, Gurbiel R, Gwozdzinski K, Trojanowski Z. The effects of in vivo and in vitro non-enzymatic glycosylation and glycoxidation on physico-chemical properties of haemoglobin in control and diabetic patients. Int J Biochem Cell Biol 1996;28(12):1393–1403.PubMedCrossRefGoogle Scholar
  123. 123.
    Duraisamy Y, Slevin M, Smith N, et al. Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes. Angiogenesis 2001;4(4):277–288.PubMedCrossRefGoogle Scholar
  124. 124.
    Ido Y, Chang KC, Lejeune WS, et al. Vascular dysfunction induced by AGE is mediated by VEGF via mechanisms involving reactive oxygen species, guanylate cyclase, and protein kinase C. Microcirculation 2001;8(4):251–263.PubMedCrossRefGoogle Scholar
  125. 125.
    Portero-Otin M, Pamplona R, Bellmunt MJ, et al. Advanced glycation end product precursors impair epidermal growth factor receptor signaling. Diabetes 2002;51(5):1535–1542.PubMedCrossRefGoogle Scholar
  126. 126.
    Twigg SM, Joly AH, Chen MM, et al. Connective tissue growth factor/IGF-binding protein-related protein-2 is a mediator in the induction of fibronectin by advanced glycosylation end-products in human dermal fibroblasts. Endocrinology 2002;143(4):1260–1269.PubMedCrossRefGoogle Scholar
  127. 127.
    Imani F, Horii Y, Suthanthiran M, et al. Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon gamma: role in tissue remodeling. J Exp Med 1993;178(6):2165–2172.PubMedCrossRefGoogle Scholar
  128. 128.
    Collison KS, Parhar RS, Saleh SS, et al. RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). J Leukoc Biol 2002;71(3):433–444.PubMedGoogle Scholar
  129. 129.
    Bernheim J, Rashid G, Gavrieli R, Korzets Z, Wolach B. In vitro effect of advanced glycation end-products on human polymorphonuclear superoxide production. Eur J Clin Invest 2001;31(12):1064.PubMedCrossRefGoogle Scholar
  130. 130.
    Abordo EA, Westwood ME, Thornalley PJ. Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP-1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. Immunol Lett 1996;53(1):7–13.PubMedCrossRefGoogle Scholar
  131. 131.
    Daoud S, Schinzel R, Neumann A, et al. Advanced glycation endproducts: activators of cardiac remodeling in primary fibroblasts from adult rat hearts. Mol Med 2001;7(8):543–551.PubMedGoogle Scholar
  132. 132.
    Brennan M. Changes in solubility, non-enzymatic glycation, and fluorescence of collagen in tail tendons from diabetic rats. J Biol Chem 1989;264(35):20947–20952.PubMedGoogle Scholar
  133. 133.
    Portero-Otin M, Pamplona R, Bellmunt MJ, et al. Advanced glycation end product precursors impair epidermal growth factor receptor signaling. Diabetes 2002;51(5):1535–1542.PubMedCrossRefGoogle Scholar
  134. 134.
    Kochakian M, Manjula BN, Egan JJ. Chronic dosing with aminoguanidine and novel advanced glycosylation end product-formation inhibitors ameliorates cross-linking of tail tendon collagen in STZ-induced diabetic rats. Diabetes 1996;45(12):1694–1700.PubMedCrossRefGoogle Scholar
  135. 135.
    Teixeira AS, Caliari MV, Rocha OA, Machado RD, Andrade SP. Aminoguanidine prevents impaired healing and deficient angiogenesis in diabetic rats. Inflammation 1999;23(6):569–581.PubMedCrossRefGoogle Scholar
  136. 136.
    Teixeira AS, Andrade SP. Glucose-induced inhibition of angiogenesis in the rat sponge granuloma is prevented by aminoguanidine. Life Sci 1999;64(8):655–662.PubMedCrossRefGoogle Scholar
  137. 137.
    Yavuz D, Tugteppe H, Kaya H, et al. Effects of aminoguanidine on wound healing in a diabetic rat model. (Abstract). Diabetes 2002;51(Suppl 2):A256.Google Scholar
  138. 138.
    Eble AS, Thorpe SR, Baynes JW. Nonenzymatic glycosylation and glucose-dependent cross-linking of proteins. J Biol Chem 1983;258:9406–9412.PubMedGoogle Scholar
  139. 139.
    Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest 1991;87:432–438.PubMedGoogle Scholar
  140. 140.
    Panagiotopoulos S, O’Brien RC, Bucala R, Cooper ME, Jerums G. Aminoguanidine has an anti-atherogenic effect in the cholesterol-fed rabbit. Atherosclerosis 1998;136:125–131.PubMedCrossRefGoogle Scholar
  141. 141.
    Bucala R, Makita Z, Koschinsky T, Cerami A, Vlassara H. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci 1993;90:6434–6438.PubMedCrossRefGoogle Scholar
  142. 142.
    Zhang J, Ren S, Sun D, Shen GX. Influence of glycation on LDL-induced generation of fibrinolytic regulators in vascular endothelial cells. Arter Thromb Vasc Biol 1998;18:1140–1148.Google Scholar
  143. 143.
    Hedrick CC, Thorpe SR, Fu MX, et al. Glycation impairs high-density lipoprotein function. Diabetologia 2000;43:312–320.PubMedCrossRefGoogle Scholar
  144. 144.
    Doucet C, Huby T, Ruiz J, Chapman MJ, Thillet J. Non-enzymatic glycation of lipoprotein(a) in vitro and in vivo. Atherosclerosis 1995;118:135–143.PubMedCrossRefGoogle Scholar
  145. 145.
    Zhang J, Ren S, Shen GX. Glycation amplifies lipoprotein(a)-induced alterations in the generation of fibrinolytic regulators from human vascular endothelial cells. Atherosclerosis 2000;150:299–308.PubMedCrossRefGoogle Scholar
  146. 146.
    Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 2001;280(5):E685–E694.PubMedGoogle Scholar
  147. 147.
    Lassegue B, Clempus RE. Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 2003;285(2):R277–R297.PubMedGoogle Scholar
  148. 148.
    Palinski W, Koschinsky T, Butler SW, et al. Immunological evidence for the presence of advanced glycation end products in atherosclerotic lesions of euglycemic rabbits. Arter Thromb Vasc Biol 1995;15:571–582.Google Scholar
  149. 149.
    Vlassara H, Fuh H, Donnelly T, Cybulsky M. Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits. Mol Med 1995;1:447–456.PubMedGoogle Scholar
  150. 150.
    Vlassara H, Fuh H, Makita Z, Krungkrai S, Cerami A, Bucala R. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad Sci USA 1992;89(24):12043–12047.PubMedCrossRefGoogle Scholar
  151. 151.
    Wautier JL, Zoukourian C, Chappey O, et al. Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J Clin Invest 1996;97:238–243.PubMedGoogle Scholar
  152. 152.
    Crauwels HM, Herman AG, Bult H. Local application of advanced glycation end products and intimal hyperplasia in the rabbit collared carotid artery. Cardiovasc Res 2000;40:173–182.CrossRefGoogle Scholar
  153. 153.
    Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein crosslinking. Science 1986;232:1629–1632.PubMedCrossRefGoogle Scholar
  154. 154.
    Park I, Raman KG, Lee KJ, et al. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 1998;4:1025–1031.PubMedCrossRefGoogle Scholar
  155. 155.
    Candido R, Forbes JM, Thomas MC, et al. A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res 2003;92(7):785–792.PubMedCrossRefGoogle Scholar
  156. 156.
    Nangaku M, Miyata T, Sada T, et al. Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model. J Am Soc Nephrol 2003;14(5):1212–1222.PubMedCrossRefGoogle Scholar
  157. 157.
    Nakamura Y, Horii Y, Nishino T, et al. Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus. Am J Pathol 1993;143:1649–1656.PubMedGoogle Scholar
  158. 158.
    Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997;99:457–468.PubMedGoogle Scholar
  159. 159.
    Yamada K, Miyahara Y, Hamaguchi K, et al. Immunohistochemical study of human advanced glycation end-products in chronic renal failure. Clin Nephrol 1994;42:354–361.PubMedGoogle Scholar
  160. 160.
    Sakata N, Imanaga Y, Meng J, et al. Increased advanced glycation end products in atherosclerotic lesions of patients with end-stage renal disease. Atherosclerosis 1999;142:67–77.PubMedCrossRefGoogle Scholar
  161. 161.
    Sims TJ, Rasmussen LM, Oxlund H, Bailey AJ. The role of glycation cross-links in diabetic vascular stiffening. Diabetologia 1996;39:946–951.PubMedCrossRefGoogle Scholar
  162. 162.
    Stitt AW, He C, Friedman S, et al. Elevated AGE-modified apoB in sera of euglycemic, normolipidemic patients with atherosclerosis: relation to tissue AGE. Mol Med 1997;3:617–627.PubMedGoogle Scholar
  163. 163.
    Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care 2002;25(6):1055–1059.PubMedCrossRefGoogle Scholar
  164. 164.
    Strirban A, Sander D, Buenting C, et al. Food advanced glycation end products (AGE) acutely impair endothelial function in patienst with diabetes mellitus (abstract). Diabetes 2003;52(Suppl 1):A19Google Scholar
  165. 165.
    Winer N, Sowers JR. Vascular compliance in diabetes. Curr Diab Rep 2003;3(3):230–234.PubMedCrossRefGoogle Scholar
  166. 166.
    Odetti P, Traverso N, Cosso L, Noberasco G, Pronzato MA, Marinari UM. Good glycaemic control reduces oxidation and glycation end-products incollagen of diabetic rats. Diabetologia 1996;39(12):1440–1447.PubMedCrossRefGoogle Scholar
  167. 167.
    Odetti P, Robaudo C, Valentini S, et al. Effect of a new vitamin E-coated membrane on glycoxidation during hemodialysis. Contrib Nephrol 1999;127:192–199.PubMedGoogle Scholar
  168. 168.
    Nakayama M, Izumi G, Nemoto Y, et al. Suppression of N(epsilon)-(carboxymethyl)lysine generation by the antioxidant N-acetylcysteine. Perit Dial Int 1999;19(3):207–210.PubMedGoogle Scholar
  169. 169.
    Trachtman H, Futterweit S, Prenner J, Hanon S. Antioxidants reverse the antiproliferative effect of high glucose and advanced glycosylation end products in cultured rat mesangial cells. Biochem Biophys Res Commun 1994;199(1):346–352.PubMedCrossRefGoogle Scholar
  170. 170.
    Kunt T, Forst T, Wilhelm A, et al. Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci (Lond) 1999;96(1):75–82.CrossRefGoogle Scholar
  171. 171.
    Jakus V, Hrnciarova M, Carsky J, Krahulec B, Rietbrock N. Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity. Life Sci 1999;65(18–19):1991–1993.PubMedCrossRefGoogle Scholar
  172. 172.
    Hammes HP, Bartmann A, Engel L, Wulfroth P. Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine. Diabetologia 1997;40(6):629–634.PubMedCrossRefGoogle Scholar
  173. 173.
    Zhao W, Devamanoharan PS, Varma SD. Fructose-mediated damage to lens alpha-crystallin: prevention by pyruvate. Biochim Biophys Acta 2000;1500(2):161–168.PubMedGoogle Scholar
  174. 174.
    Varma SD, Ramachandran S, Devamanoharan PS, Morris SM, Ali, AH. Prevention of oxidative damage to rat lens by pyruvate in vitro: possible attenuation in vivo. Curr Eye Res 1995;14(8):643–649.PubMedGoogle Scholar
  175. 175.
    Forbes JM, Soulis T, Thallas V, et al. Renoprotective effects of a novel inhibitor of advanced glycation. Diabetologia 2001;44(1):108–114.PubMedCrossRefGoogle Scholar
  176. 176.
    Wilkinson-Berka JL, Kelly DJ, Koerner SM, et al. ALT-946 and aminoguanidine, inhibitors of advanced glycation, improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat. Diabetes 2002;51(11):3283–3289.PubMedCrossRefGoogle Scholar
  177. 177.
    Oturai PS, Christensen M, Rolin B, Pedersen KE, Mortensen SB, Boel E. Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats. Metabolism 2000;49(8):996–1000.PubMedCrossRefGoogle Scholar
  178. 178.
    Booth AA, Khalifah RG, Todd P, Hudson BG. In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs). Novel inhibition of post-Amadori glycation pathways. J Biol Chem 1997;272(9):5430–5437.PubMedCrossRefGoogle Scholar
  179. 179.
    Pomero F, Molinar, Min A, et al. Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose. Acta Diabetol 2001;38(3):135–138.PubMedCrossRefGoogle Scholar
  180. 180.
    Stracke H, Hammes HP, Werkmann D, et al. Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats. Exp Clin Endocrinol Diabetes 2001;109(6):330–336.PubMedCrossRefGoogle Scholar
  181. 181.
    Onorato JM, Jenkins AJ, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. Mechanism of action of pyridoxamine. J Biol Chem 2000;275(28):21177–21184.PubMedCrossRefGoogle Scholar
  182. 182.
    Stitt A, Gardiner TA, Anderson NL, et al. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 2002;51(9):2826–2832.PubMedCrossRefGoogle Scholar
  183. 183.
    Degenhardt TP, Alderson NL, Arrington DD, et al. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int 2002;61(3):939–950.PubMedCrossRefGoogle Scholar
  184. 184.
    Nakamura S, Makita Z, Ishikawa S, et al. Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195, a novel inhibitor of advanced glycation. Diabetes 1997;46(5):895–899.PubMedCrossRefGoogle Scholar
  185. 185.
    Wada R, Nishizawa Y, Yagihashi N, et al. Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy. Eur J Clin Invest 2001;31(6):513–520.PubMedCrossRefGoogle Scholar
  186. 186.
    Mizutani K, Ikeda K, Tsuda K, Yamori Y. Inhibitor for advanced glycation end products formation attenuates hypertension and oxidative damage in genetic hypertensive rats. J Hypertens 2002;20(8):1607–1614.PubMedCrossRefGoogle Scholar
  187. 187.
    Schwedler SB, Verbeke P, Bakala H, et al. N-phenacylthiazolium bromide decreases renal and increases urinary advanced glycation end products excretion without ameliorating diabetic nephropathy in C57BL/6 mice. Diabetes Obes Metab 2001;3(4):230–239.PubMedCrossRefGoogle Scholar
  188. 188.
    Vaitkevicius PV, Lane M, Spurgeon H, et al. A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci USA 2001;98(3):1171–1175.PubMedCrossRefGoogle Scholar
  189. 189.
    Cohen MP, Clements RS, Cohen JA, Shearman CW. Prevention of decline in renal function in the diabetic db/db mouse. Diabetologia 1996;39(3):270–274.PubMedCrossRefGoogle Scholar
  190. 190.
    Cohen MP, Sharma K, Jin Y, et al. Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy. J Clin Invest 1995;95(5):2338–2345.PubMedCrossRefGoogle Scholar
  191. 191.
    Sebekova K, Schinzel R, Munch G, Krivosikova Z, Dzurik R, Heidland A. Advanced glycation end-product levels in subtotally nephrectomized rats: beneficial effects of angiotensin II receptor 1 antagonist losartan. Miner Electrolyte Metab 1999;25(4–6):380–383PubMedGoogle Scholar
  192. 192.
    Miyata T, van Y, persele de Strihou C, et al. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol 2002;13(10):2478–2487.PubMedCrossRefGoogle Scholar
  193. 193.
    Parving HH, Hommel E, Jensen BR, Hansen HP. Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients. Kidney Int 2001;60(1):228–234.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Melpomeni Peppa
    • 1
  • Jaime Uribarri
    • 2
  • Helen Vlassara
    • 1
  1. 1.Department of GeriatricsMount Sinai School of MedicineNew York
  2. 2.Division of NephrologyMount Sinai School of MedicineNew York

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